RESUMEN
Stereotactic gamma knife radiosurgery (GKS) may induce a transient enlargement of vestibular schwannomas (VS). This phenomenon, known as pseudoprogression or swelling, starts at about 3 months following GKS, peaks at about 6 months, and typically subsides thereafter, usually without significant neurological deterioration. We describe a 34-year-old female who developed an aggressive enlargement of a VS 1 month after GKS. The patient was treated with an immediate external ventricular drainage and surgical resection via retrosigmoid approach for an acute neurological deterioration due to hydrocephalus and brainstem compression. Histopathological examination revealed a VS with abundant intratumoral thrombosis and necrosis, suggesting that its rapid expansion could be related to massive radiation-induced tumor necrosis. The present case indicated that rapid life-threating enlargement of a VS may occur as an early complication following GKS.
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Hidrocefalia/etiología , Neoplasias Inducidas por Radiación/etiología , Neuroma Acústico/etiología , Radiocirugia/efectos adversos , Adulto , Tronco Encefálico/patología , Tronco Encefálico/cirugía , Femenino , Humanos , Hidrocefalia/patología , Hidrocefalia/cirugía , Neoplasias Inducidas por Radiación/patología , Neoplasias Inducidas por Radiación/cirugía , Neuroma Acústico/patología , Neuroma Acústico/cirugíaRESUMEN
BACKGROUND: Patients with low-grade gliomas (LGGs) with isocitrate dehydrogenase (IDH) mutation (mut) and 1p19q codeletion (codel) have a median overall survival of longer than 10 years. The aim of this study is to assess the role of postsurgical treatments. SUBJECTS, MATERIALS, AND METHODS: We evaluated patients with LGGs with IDH mut and 1p19q codel; IDH1/2 was performed by immunohistochemistry and quantitative polymerase chain reaction. In all wild-type cases, we performed next-generation sequencing. 1p19 codel analysis was performed by fluorescence in situ hybridization. RESULTS: Among the 679 patients, 93 with LGGs with IDH mutation and 1p19q codel were included. Median follow-up (FU) was 96.1 months. Eighty-four patients (90.3%) were high risk according to Radiation Therapy Oncology Group criteria. After surgery, 50 patients (53.7%) received only FU, 17 (18.3%) chemotherapy (CT), and 26 (30.1%) radiotherapy (RT) with (RT + CT, 8 patients, 8.6%) or without (RT, 18 patients, 19.4%) chemotherapy. Median progression-free survival (mPFS) was 46.3 months, 50.8 months, 103.6 months, and 120.2 months in patients with FU alone, with CT alone, with RT alone, or with RT + CT, respectively. Median PFS was significantly longer in patients who received postsurgical treatment (79.5 months, 95% confidence interval [CI]: 66.4-92.7) than patients who received FU (46.3 months, 95% CI: 36.0-56.5). Moreover, mPFS was longer in patients who received RT (alone or in combination with CT, n = 26, 113.8 months, 95% CI: 57.2-170.5) than those who did not (n = 67, 47.3 months, 95% CI: 36.4-58.2). In particular, temozolomide alone did not improve PFS with respect to FU. CONCLUSION: RT with or without chemotherapy, but not temozolomide alone, could extend PFS in IDH mut 1p19q codel LGGs. IMPLICATIONS FOR PRACTICE: Low-grade gliomas with high-risk features, defined according to Radiation Therapy Oncology Group criteria, receive radiotherapy and/or chemotherapy as postsurgical treatments. Radiotherapy, however, has serious long-term effects (cognitive impairment), which are to be taken into account in these young patients. Moreover, low-grade gliomas with isocitrate dehydrogenase mutation and 1p19q codeletion (oligodendrogliomas) have an extremely long survival and a better prognosis. This study suggests that postsurgical treatments prolong the time before tumor progression in patients with good prognosis as well as those with oligodendroglioma. Moreover, temozolomide alone might not be effective in prolonging progression-free survival.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/terapia , Oligodendroglioma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/patología , Encéfalo/cirugía , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Quimioradioterapia Adyuvante/métodos , Quimioradioterapia Adyuvante/estadística & datos numéricos , Quimioterapia Adyuvante/métodos , Quimioterapia Adyuvante/estadística & datos numéricos , Cromosomas Humanos Par 1/genética , Femenino , Estudios de Seguimiento , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Oligodendroglioma/genética , Oligodendroglioma/mortalidad , Oligodendroglioma/patología , Supervivencia sin Progresión , Temozolomida/uso terapéuticoRESUMEN
AIM: To evaluate relevance of clinical and molecular factors in adult low-grade gliomas (LGG) and to correlate with survival. METHODS: We reviewed records from adult LGG patients from 1991 to 2015 who received surgery and had sufficient tissue to molecular biomarkers characterization. RESULTS: 213 consecutive LGG patients were included: 17.4% were low-risk, according to Radiation Therapy Oncology Group (RTOG) risk assessment. IDH 1/2 mutation, 1p/19q co-deletion, MGMT methylation were found in 93, 50.8 and 65.3% of patients. Median follow-up was 98.3 months. In univariate analysis, overall survival was influenced by extent of resection (p = 0.011), IDH mutation (p < 0.001), 1p/19q co-deletion (p = 0.015) and MGMT methylation (p = 0.013). In multivariate analysis, RTOG clinical risk (p = 0.006), IDH mutation (p < 0.001) and 1p/19q co-deletion (p = 0.035) correlated with overall survival. RTOG clinical risk (p = 0.006), IDH mutation (p < 0.001) and 1p/19q co-deletion (p = 0.035) correlated with overall survival. CONCLUSION: Both clinical and molecular factors are essential to determine prognosis and treatment strategies.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Glioma/genética , Glioma/mortalidad , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/terapia , Deleción Cromosómica , Cromosomas Humanos Par 1 , Estudios de Cohortes , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Femenino , Glioma/terapia , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Procedimientos Neuroquirúrgicos , Pronóstico , Factores de Riesgo , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: MGMT methylation status represents a powerful prognostic factor in newly diagnosed glioblastoma (GBM). Recently, its role in recurrent tumors has also been suggested; however, few data investigating the stability of this biomarker during the clinical course of the disease are available. In this study, we evaluated the rate of change of MGMT methylation status between diagnosis and first recurrence in patients who received tumor resection for recurrent GBM. METHODS: We included patients who received temozolomide concurrent with and adjuvant to radiotherapy after diagnosis of GBM and had a second surgery performed at least 3 months after radiotherapy completion. Other eligibility criteria were age ≥18 years and Eastern Cooperative Oncology Group performance status 0-2. We evaluated the MGMT methylation status by methylation-specific polymerase chain reaction. RESULTS: From our institutional data warehouse, 295 patients with recurrent GBM who underwent second surgery were evaluated. MGMT methylation status at both first and second surgery was available for 108 patients. MGMT was methylated in both surgeries in 38 patients (35.2%), while it was unmethylated in 43 patients (39.8%). We found a significant concordance between the first and the second MGMT methylation assessments (K = 0.500, p < .001), MGMT methylation being stable in 75% of the cases. CONCLUSION: MGMT methylation presents relative stability during the clinical course of GBM. The Oncologist 2017;22:432-437 IMPLICATIONS FOR PRACTICE: MGMT methylation is a prognostic factor in newly diagnosed glioblastoma. In this study, we evaluated the rate of change of MGMT methylation during the clinical course of the disease, and we found a significant concordance between the first and the second MGMT methylation assessments, with MGMT methylation being stable in 75% of the cases. Thus, re-testing this biomarker at recurrence does not provide further information for clinicians. MGMT methylation at first surgery, extent of resection at second surgery, and time between first and second surgery are significantly correlated with overall survival. Age and extent of resection are correlated with post-progression survival.
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Metilación de ADN/genética , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Glioblastoma/genética , Pronóstico , Proteínas Supresoras de Tumor/genética , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/genética , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Glioblastoma/diagnóstico , Glioblastoma/patología , Glioblastoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Regiones Promotoras Genéticas , TemozolomidaRESUMEN
BACKGROUND: Ovarian cancer is metastatic at presentation in about 62% of cases, but brain metastases are rare, reported in 3.3-4% of patients. Brain metastasis seems to be more frequent in advanced stages at diagnosis and in patients with BRCA1/2 mutation. CASE PRESENTATION: We present a case of a 47-year-old Caucasian woman, BRCA wild type, with an ovarian cancer that started with single cerebellar metastasis. CONCLUSION: Brain metastases in ovarian cancer are rare and complex for diagnosis and management. This case focuses both on diagnosis and treatment, emphasizing the importance of a multimodal approach in a multidisciplinary team.
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Neoplasias Encefálicas , Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ováricas/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/genéticaRESUMEN
BACKGROUND: Temozolomide (TMZ) is safe and effective in the treatment of aggressive pituitary adenomas (PAs). However, the optimal duration of TMZ therapy is still unknown. Moreover, data about administration of TMZ in elderly (≥65 years) people to treat aggressive PAs are scarce. We report the case of the oldest female patient undergoing the longest TMZ protocol described so far to treat an aggressive, initially silent corticotroph PA. CASE REPORT: The patient initially underwent partial surgical removal of the PA. Subsequent treatment with cabergoline was applied, but it was unsuccessful in controlling the growth of the residual tumor. Pasireotide and external radiation also showed to be ineffective; therefore, treatment with TMZ was started at the standard dose of 200 mg/m2/day for 5 days every 4 weeks for a total of 47 cycles. At the time of treatment's beginning, the patient was 83 years old. Radiological follow-up documented a progressive, remarkable reduction of the adenoma and the last imaging, after 39 cycles of TMZ, showed an intrasellar lesion with large areas of cystic degeneration. The patient also developed adrenal deficiency managed with glucocorticoid replacement. No major side effects were observed throughout the treatment, with exception of nausea, well controlled with anti-emetic medication. TMZ therapy was discontinued after 47 cycles; hormonal and imaging follow-up investigations documented sustained functional and dimensional response. CONCLUSIONS: Our case supports the long-term use of TMZ, confirming its safety and efficacy also for elderly patients.
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BACKGROUND: Chordomas are rare primary tumors of the bone that arise from embryonic notochord. They are locally aggressive tumors with a high tendency for postsurgical recurrence. On the other hand, distant metastases are rare. When they occur, they involve lungs, liver, lymph nodes, and bones. Skin and subcutaneous tissue involvement is even rarer and usually occurs by direct extension of the primary tumor or by local recurrence. Distant cutaneous metastasis from chordoma is an exceptional finding, with fewer than 20 cases reported in the literature. All the cutaneous metastases described derive from sacral chordomas, except for 2 cases in which the source of metastasis is skull-base chordomas. CASE DESCRIPTION: We report the case of a 55-year-old man with skin metastasis from a cervical chordoma. CONCLUSIONS: Metastasis has to be taken into account in the differential diagnosis when a new skin lesion appears in a patient with a past medical history of chordoma. To the best of our knowledge, this is the first case of cutaneous metastasis from spinal cervical chordoma. A systematic literature review was performed.
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Vértebras Cervicales/diagnóstico por imagen , Cordoma/secundario , Neoplasias Cutáneas/secundario , Neoplasias de la Columna Vertebral/patología , Vértebras Cervicales/cirugía , Cordoma/diagnóstico por imagen , Cordoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Neoplasias Cutáneas/cirugía , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Surrogate molecular classification identifies different subtypes of invasive breast carcinoma on the basis of their immunohistochemical markers. The purpose of the study is to verify whether the immunohistochemical markers and surrogate molecular subtypes can be correctly assessed on the core needle biopsy (CNB) when compared with the corresponding surgical excision (SE), with or without neoadjuvant treatment (NAT). Cases with invasive carcinomas identified on both CNB and SE were retrospectively selected. With immunohistochemistry for estrogen receptors (ER), progesterone receptors (PgR), Ki67, human epidermal growth factor receptor 2 (Her2), and molecular analysis for Her2, surrogate molecular classification was determined in 4 and 5 groups, according to the 2013 St Gallen consensus. A total of 1067 cases was considered and complete data for surrogate molecular classification were available for 988 cases (655 without NAT, 333 with NAT). Without NAT, concordance was strong for ER and Her2, moderate for PgR, and weak for Ki67; concordance for surrogate molecular classification was moderate. After NAT, lower concordance rates were recorded, with significant reduction of PgR (P<0.001) and Ki67 (P<0.001). Without NAT, the surrogate molecular subtypes of breast carcinoma can be reliably assessed on CNB; Ki67 and/or PgR may be repeated on SE when values are close to cutoffs to avoid tumor subtype misclassification. After NAT, it seems advisable to repeat at least Ki67 and PgR.
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Neoplasias de la Mama/metabolismo , Antígeno Ki-67/metabolismo , Terapia Neoadyuvante , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Biopsia con Aguja Gruesa , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estudios RetrospectivosRESUMEN
BACKGROUND: Diffuse grade II and grade III gliomas are actually classified in accordance with the presence of isocitrate dehydrogenase mutation (IDH-mut) and the deletion of both 1p and 19q chromosome arms (1p/19q codel). The role of tumour grading as independent prognostic factor in these group of tumours remains matter of debate. The aim of this study was to determine if grade is an independent prognostic factor and not somehow associated to IDH mutation and 1p/19q status of the tumour. METHODS: We analysed 399 consecutive patients with newly diagnosed, histologically proven World Health Organisation (WHO) 2016 grade II or grade III IDH-mut gliomas, assessed by polymerase chain reaction, immunohistochemistry or next-generation sequencing (NGS). RESULTS: The analysis included 399 patients with grade II (n = 250, 62.7%) or grade III (n = 149, 37.3%) diffuse gliomas. Median follow-up time was 105.3 months. Median survival was 148.1 months. In multivariate analysis, grade II (hazard ratio [HR] = 0.342, 95% confidence interval [CI]: 0.221-0.531; P < 0.001) and 1p/19q codeletion (HR = 0.440, 95% CI: 0.290-0.668; P < 0.001) were independently associated with a lower risk for death. The difference in survival remained significant (p = 0.006 in astrocytomas, p = 0.014 in oligodendrogliomas) when adjusted for histological subtype. Residual disease after surgery (or biopsy) negatively affected survival (HR: 2.151, 95% CI: 1.375-3.367, P = 0.001). Post-surgical treatment with radiotherapy + adjuvant chemotherapy improved survival compared with follow-up and other treatments (HR: 0.316, 95% CI: 0.156-0.641, P = 0.001). CONCLUSIONS: In our study, histopathological grade still affects survival in IDH-mutant WHO grade II and III diffuse gliomas. This effect appears to be independent from molecular features, extension of surgical resection and post-surgical treatments. Therefore, physicians should continue to take into account tumour grade, along their molecular characteristics, for a better clinical and therapeutic management of the patients.
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Neoplasias Encefálicas/fisiopatología , Glioma/fisiopatología , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Femenino , Glioma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Adulto JovenRESUMEN
INTRODUCTION: Tailgut cyst are congenital cystic lesion arising from remnant of the embryological postnatal gut. Tailgut cyst are multinodular, uncapsulated and usually well-circumscribed. Presacral cysts are rare in adult and most of the lesions are benign. Malignant degeneration can occur, however is extremely rare. CASE REPORT: We present the case of a 74 years old woman with slow increase in size and malignant degeneration of a tailgut cyst. Five years before, during the follow up after mastectomy for cancer, she manifested rise of CA 19-9 tumor marker and a presacral cystic collection on thoraco-abdominal CT. She was followed with CT and MRI that showed that the cyst, with a solid component of the wall, was growing larger. After a five-year evolution, the cyst was resected. The histological examination on the solid component demonstrated intestinal adenocarcinoma. CONCLUSION: MRI ant TC can play essential role in the preoperative detection and characterization for the differential diagnosis, treatment strategies and evaluate neoplastic degeneration. Due to the risk of malignancy surgical resection must be performed after the diagnosis. Surgical therapy is mandatory when the cyst grow larger and a solid component is present. KEY WORDS: Presacral cyst, Retrorectal tumors, Tailgut cyst.
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Adenocarcinoma/patología , Quistes/patología , Neoplasias Intestinales/patología , Adenocarcinoma/sangre , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/cirugía , Anciano , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/terapia , Antígeno CA-19-9/sangre , Carcinoma Ductal de Mama/terapia , Transformación Celular Neoplásica , Terapia Combinada , Quistes/sangre , Quistes/congénito , Quistes/cirugía , Diagnóstico Tardío , Endosonografía , Femenino , Hamartoma/congénito , Hamartoma/patología , Hamartoma/cirugía , Humanos , Neoplasias Intestinales/sangre , Neoplasias Intestinales/diagnóstico por imagen , Neoplasias Intestinales/cirugía , Imagen por Resonancia Magnética , Neoplasias Primarias Secundarias/sangre , Neoplasias Primarias Secundarias/patología , Tomografía Computarizada por Rayos XRESUMEN
We report on the magnetic resonance spectroscopy (MRS) characterisation of different human meningiomas. Three histological subtypes of meningiomas (meningothelial, fibrous and oncocytic) were analysed both through in vivo and ex vivo MRS experiments. The ex vivo high-resolution magic angle spinning (HR-MAS) investigations, permitting an accurate description of the metabolic profile, are very helpful for the assignment of the resonances in vivo of human meningiomas and for the validation of the quantification procedure of in vivo MR spectra. By using one- and two-dimensional experiments, we were able to identify several metabolites in different histological subtypes of meningiomas. Our spectroscopic data confirmed the presence of the typical metabolites of these benign neoplasms and, at the same time, that meningomas with different morphological characteristics have different metabolic profiles, particularly regarding macromolecules and lipids. The ex vivo spectra allowed a better understanding and interpretation of the in vivo MR spectra, showing that the HR-MAS MRS technique could be a complementary method to strongly support the in vivo MR spectroscopy and increase its clinical potentiality.
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Biomarcadores de Tumor/análisis , Espectroscopía de Resonancia Magnética/métodos , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Análisis EspectralRESUMEN
We hypothesised that apolipoprotein E (apoE) influences brain tumours by delivery of lipids to tumour cells and by analogy with other brain insults. APOE gene analysis was performed for 126 glioblastomas, the commonest primary brain tumour. Neither APOE epsilon2 nor epsilon4 alleles were significantly associated with differences in post-operative survival. However, there was apoE immunoreactivity of tumour cells, macrophages in areas of necrosis and astrocytes nearby. The immunohistochemistry findings support the hypothesis that apoE is involved in the delivery of lipids to tumour cells and in the recycling of lipids by macrophages in necrotic areas, raising the possibility that apoE-mediated lipid transport may represent a new therapeutic target in brain tumours.
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Apolipoproteínas E/fisiología , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Alelos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/terapia , Genotipo , Glioblastoma/cirugía , Glioblastoma/terapia , Humanos , Inmunohistoquímica , Metabolismo de los Lípidos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients ≤aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.
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AIMS AND BACKGROUND: Recursive partioning analysis (RPA) is commonly used to define the stratification of patients with glioblastoma. Epigenetic silencing of the O6-methylguanine methyltransferase (MGMT) gene by promoter methylation plays an important role in regulating MGMT expression in gliomas and this is an established independent prognostic factor. We tested a prognostic scoring system including all clinical variables used by RPA classification (age, ECOG performance status and type of surgery) and MGMT gene promoter methylation status. METHODS: Seventy-eight consecutive patients with newly diagnosed, histopathologically confirmed conventional glioblastoma were included. Information about MGMT promoter methylation status was available for all of them. Based on the patients' age (<50 vs ≥50 years), ECOG performance status (0 vs ≥1), type of surgery (gross tumor resection versus partial resection/biopsy) and MGMT promoter methylation status (methylated versus unmethylated), three classes of risk were generated where the prognostic score was defined assigning 1 point to every favorable parameter (Class I: ≥3; Class II: 2; Class III: 0-1). All classes were correlated with overall survival. RESULTS: The median survival times were 32.4, 8.6 and 8.8 months for Class I, II and III, respectively, corresponding to 2-year survival rates of 69%, 13.5% and <1%. The same analysis was performed on 54 patients treated with postoperative concomitant chemoradiotherapy. The median survival times were 32.5, 13.4 and 8.9 months for Class I, II and III, respectively, corresponding to 2-year survival rates of 68.6%, 26.9% and <1%. In both groups of 78 and 54 patients the differences in survival between Class I and III were statistically significant ( P <0.0001). CONCLUSIONS: The proposed prognostic scoring system including clinical variables and MGMT promoter methylation status proved valuable in patients with primary conventional glioblastoma, especially those treated with postoperative chemoradiotherapy.
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Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/mortalidad , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Glioblastoma/diagnóstico , Glioblastoma/mortalidad , Proteínas Supresoras de Tumor/metabolismo , Neoplasias del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/cirugía , Quimioradioterapia Adyuvante , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Glioblastoma/metabolismo , Glioblastoma/cirugía , Humanos , Italia/epidemiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Regiones Promotoras Genéticas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Proteínas Supresoras de Tumor/genéticaRESUMEN
AIMS: INI1 expression and its correlation with MGMT gene promoter methylation status and follow-up was investigated in 77 surgically removed glioblastomas then treated with radiotherapy (RT) or RT plus temozolomide (TMZ). METHODS: INI1 was determined by immunohistochemistry and MGMT by methylation-specific PCR. RESULTS: INI1 was expressed in 83.1% of cases. The median overall survival (OS) was 13.6 months in INI1+ tumours and 7.2 months in INI1- tumours. 31.3% of patients with INI1+ tumours were alive compared with 15.4% of patients with INI1- tumours. MGMT methylation was detected in 31.2% of cases. OS was significantly different between patients with methylated tumours and un-methylated tumours (p < 0.04), and between patients with RT+ TMZ and RT alone (p < 0.001). Considering both treatment and MGMT, the difference in OS was significant (p < 0.002). The difference in OS according to MGMT and INI1 was significant (p < 0.04). The longest median OS was recorded among methylated and INI1+ tumours. Among un-methylated tumours, the median OS was 11.1 months in INI1+ and 6.5 months in INI1- tumours. No patients were alive with un-methylated and INI1- tumours. CONCLUSIONS: Loss of INI1 immunohistochemical expression in glioblastoma may be indicating an underlying molecular aberration accounting for the more aggressive clinical behaviour.